Safety Study of KPT-330 (Selinexor) in Patients With Advanced or Metastatic Solid Tumor Cancer

NCT01607905 | Completed Phase 1 Results FDA Drug

• 1 other identifier: KCP-330-002
• Study Type: interventional
• Target: 192
• Locations: 3 countries
• Sites: 6

Brief Summary

Phase 1 study to evaluate the safety and tolerability of selinexor and determine the Recommended Phase 2 Dose (RP2D) of selinexor for advanced or metastatic solid tumor malignancies.

Conditions

Solid Tumor

Keywords

Selinexor; KPT-330; Squamous Cell Carcinoma; Glioblastoma multiforme; Adenocarcinoma; Melanoma; Colorectal cancer; Gynecological cancer; Castrate-resistant Prostate Cancer; Other solid tumors

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

  An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. TEAE was defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event (SAE) was defined as an AE that meets one or more of the mentioned criteria; is fatal, life threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly/birth defect, or important medical events. Number of participants with TEAEs and TESAEs were reported.

  From start of study drug administration to 30 days after last dose of study treatment (maximum duration of 45 months)

• Number of Participants With Treatment-related Treatment-emergent Adverse Events

  An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. TEAE was defined as an adverse event with an onset that occurs after receiving study drug. A treatment-related AE was any untoward medical occurrence in a clinical investigation participant administered a medicinal product; the event had a causal relationship with the treatment or usage.

  From start of study drug administration to 30 days after last dose of study treatment (maximum duration of 45 months)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) Greater Than or Equal to Grade 3, Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03

  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. A treatment related AE was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage.

  From start of study drug administration to 30 days after last dose of study treatment (maximum duration of 45 months)

• Number of Participants Who Experienced Dose Limiting Toxicity (DLT)

  Evaluation of DLTs was only conducted in participants who participated in the Dose-escalation Phase. A DLT was defined as any of the following, considered possibly related to drug administration, occurring in the first 28 days (or 21 days for participants on Schedule 8) at the target dose (ie, for Schedule 2 this meant the first 4 weeks after the 12 mg/m2 run-in week): Missed selinexor doses due to drug-related toxicities, discontinuation of a participant due to a toxicity that was at least possibly related to study drug before completing Cycle 1.

  Cycle 1 only (28-day cycle)

• Recommended Phase 2 Dose (RP2D)

  The RP2D was the maximum tolerated dose (MTD) or less. MTD was defined as the next lower dose level below the one in which \>1 of 3 participants or ≥2 of 6 participants experienced DLT, provided that dose level was ≤25 percent (%) lower than the highest (intolerable) dose tested. If the projected MTD was \>25% lower than the highest dose tested, then an additional cohort of ≥3 participants was added at a dose that was intermediate between the intolerable dose and the next lower dose.

  From start of study drug administration to 30 days after last dose of study treatment (maximum duration of 45 months)

Secondary Outcomes (12)

• Maximum Observed Plasma Concentration (Cmax) of Selinexor

  Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes

• Time of Maximum Observed Concentration in Plasma (Tmax) of Selinexor

  Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes

• Area Under the Concentration Time Curve From the Time of Dosing to Time in Plasma (AUC0-t) of Selinexor

  Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes

• Area Under the Concentration Time Curve From the Time of Dosing Extrapolated to Infinity (AUC0-inf) of Selinexor

  Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes

• Elimination Half-Life (t1/2) of Selinexor

  Cycle1, Day1: Pre-dose, 30, 60, 120, 240, 480 minutes

Study Arms (7)

Arm A (Colorectal Cancer)

EXPERIMENTAL

Participants with colorectal cancer and liver metastasis received oral selinexor as single agent in 8 schedules, Schedule1: ≤12milligrams per meter square(mg/m\^2) 3 times weekly(TIW) during Weeks 1 and 3, twice weekly(BIW) during Weeks 2 and 4 up to 10 doses/cycle(28 days/cycle); Schedule2: \>12mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle(28 days/cycle); Schedule3: ≥30mg/m\^2 BIW(Days 1 and 3) up to 8 doses/cycle(28 days/cycle); Schedule4: ≥20mg/m\^2 BIW(Days 1 and 2) up to 8 doses/cycle(28 days/cycle); Schedule5: ≥35mg/m\^2 BIW(Days 1 and 4) up to 8 doses(28 days/cycle); Schedule6: ≥20mg/m\^2 BIW(Days 1 and 4) after 500 mg(Week 1) to 1000 mg(Week 2 onwards) acetaminophen(given 1 hour prior to each selinexor dose) up to 8 doses/cycle (28 days/cycle); Schedule7: ≥50mg/m\^2 once weekly(QW) up to 4 doses/cycle(28 days per cycle); Schedule8: ≥45mg/m\^2 BIW(Days 1 and 3) up to 4 doses/cycle(21 days/cycle), until disease progression, death, or unacceptable toxicity.

Drug: Selinexor; Drug: Acetaminophen

Arm B (Gynecological Cancer)

EXPERIMENTAL

Participants with gynecological cancer received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m\^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: \>12 mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m\^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m\^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m\^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m\^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m\^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity.

Drug: Selinexor

Arm C (Squamous Cell Cancer)

EXPERIMENTAL

Participants with squamous cell cancer received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m\^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: \>12 mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m\^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m\^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m\^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m\^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m\^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity.

Drug: Selinexor

Arm D (Castrate-resistant Prostate Cancer)

EXPERIMENTAL

Participants with castrate-resistant prostate cancer (CRPC) received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m\^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: \>12 mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m\^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m\^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m\^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m\^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m\^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity.

Drug: Selinexor

Arm E (Glioblastoma Multiforme)

EXPERIMENTAL

Participants with glioblastoma multiforme (GBM) received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m\^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: \>12 mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m\^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m\^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m\^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m\^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m\^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity.

Drug: Selinexor

Arm F (Melanoma)

EXPERIMENTAL

Participants with Melanoma received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m\^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: \>12 mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m\^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m\^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m\^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m\^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m\^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity.

Drug: Selinexor

Arm G (Other Solid Tumors)

EXPERIMENTAL

Participants with other solid tumors received oral selinexor as a single agent in eight schedules, Schedule 1: ≤12 mg/m\^2 TIW during Weeks 1 and 3, BIW during Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 2: \>12 mg/m\^2 TIW during Weeks 1 and 3, BIW in Weeks 2 and 4 up to 10 doses/cycle (28 days/cycle); Schedule 3: ≥30 mg/m\^2 BIW (Days 1 and 3) up to 8 doses/cycle (28 days/cycle); Schedule 4: ≥20 mg/m\^2 BIW (Days 1 and 2) up to 8 doses/cycle (28 days/cycle); Schedule 5: ≥35 mg/m\^2 BIW (Days 1 and 4) up to 8 doses (28 days/cycle); Schedule 7: ≥50 mg/m\^2 QW up to 4 doses/cycle (28 days per cycle); Schedule 8: ≥45 mg/m\^2 BIW (Days 1 and 3) up to 4 doses/cycle (21 days/cycle), until disease progression, death, or unacceptable toxicity.

Drug: Selinexor

Interventions

Selinexor DRUG

Participants in this study will receive selinexor orally at dose levels specified for their respective dose cohorts. Dosing will begin at 3 mg/m\^2 twice a week and will escalate until the MTD or RP2D is determined. Cycles will be repeated in 4-week (28 days for schedule 1 to 7) and 3-week (21 days for schedule 8) intervals until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, dose adjustment will be permitted.

Also known as: KPT-330, XPOVIO

Arm A (Colorectal Cancer); Arm B (Gynecological Cancer); Arm C (Squamous Cell Cancer); Arm D (Castrate-resistant Prostate Cancer); Arm E (Glioblastoma Multiforme); Arm F (Melanoma); Arm G (Other Solid Tumors)

Acetaminophen DRUG

Oral 500 mg (in Cycle 1, Week 1) to 1000 mg (in Cycle 1, Week 2 and onwards) of acetaminophen will be administered 1 hour prior to each selinexor dose up to 8 doses per cycle (28 days per cycle)

Arm A (Colorectal Cancer)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Dose Escalation Phase: Patients with advanced or metastatic solid tumors for which no standard therapy is available. For Schedule 6 only: patients with colorectal cancer with liver metastasis.
• Dose Expansion Phase: Previously treated, metastatic or advanced recurrent malignancy with 1 of the following diagnoses, which has been confirmed histologically or cytologically:
• Up to 12 patients with metastatic colorectal cancer with a history of progression or recurrence following prior fluoropyrimidine, irinotecan and platinum containing regimens as well as bevacizumab. In addition, patients with Kras wild type tumor must have received at least one EGFR blocker.
• Up to 6 patients with histological or cytological documentation of advanced ovarian, fallopian tube, or primary peritoneal carcinoma with a history of progression or recurrence following at least one prior platinum and one taxane based chemotherapy
• Up to 12 patients with incurable Squamous cell cancers as follows:
• A minimum of 4 Squamous Non-Small Cell Lung Cancer (Sq-NSCLC)
• A minimum of 4 Squamous Cell Carcinomas of the Head and Neck (Sq-HNC)
• Squamous Cell Carcinoma of the Cervix (SqCC) All patient with Squamous Cell Carcinomas should have a documented history of progression or recurrence following at least one prior platinum based chemotherapy or chemotherapy/radiation containing regimen
• Up to 6 patients with castration-resistant prostate cancer (CRPC) that was pathologically confirmed as adenocarcinoma of the prostate and with evidence of metastatic disease on bone scan or other imaging. Patient must have progressive disease after at least one hormonal treatment and one cytotoxic therapy e.g. with docetaxel, mitoxantrone.
• Up to 12 patients with unresectable metastatic melanoma whose disease progressed on at least 1 prior systemic anticancer regimen (chemotherapy, biological or immunotherapy, or targeted therapy). Enrollment to this cohort may have been stopped before reaching 12 patients once the dose-escalation portion of the study was completed.
• Approximately 6 patients with advanced or metastatic solid tumors were to be enrolled on Schedule 8 at a starting dose of 35 mg/m\^2 to assess general tolerability and activity of selinexor.
• Dose Escalation Phase: Patients have exhausted, or be deemed to not benefit from, further conventional therapy and have evidence of progressive disease on study entry.

You may not qualify if:

• Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤3 weeks prior to cycle 1 day 1 and mitomycin C and radioimmunotherapy 6 weeks prior to cycle 1 day 1;
• Except for patients with GBM/ AnaA in the Expansion Phase, patients with active CNS malignancy are excluded. Asymptomatic small lesions are not considered active. Treated lesions may be considered inactive if they are stable for at least 3 months.

Sponsors & Collaborators

• Karyopharm Therapeutics Inc: lead

Study Sites (6)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Princess Margaret Hospital

Toronto, Ontario, M5T 2M9, Canada

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Related Publications (1)

• Machlus KR, Wu SK, Vijey P, Soussou TS, Liu ZJ, Shacham E, Unger TJ, Kashyap T, Klebanov B, Sola-Visner M, Crochiere M, Italiano JE Jr, Landesman Y. Selinexor-induced thrombocytopenia results from inhibition of thrombopoietin signaling in early megakaryopoiesis. Blood. 2017 Aug 31;130(9):1132-1143. doi: 10.1182/blood-2016-11-752840. Epub 2017 Jun 19.

  PMID: 28630120 DERIVED

MeSH Terms

Conditions

Carcinoma, Squamous Cell; Glioblastoma; Adenocarcinoma; Melanoma; Colorectal Neoplasms

Interventions

selinexor; Acetaminophen

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Results Point of Contact

• Title: Jatin Shah
• Organization: Karyopharm Therapeutics Inc

jshah@karyopharm.com

(617) 658-0600

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2012
• First Posted: May 30, 2012
• Study Start: June 18, 2012
• Primary Completion: March 15, 2016
• Study Completion: March 15, 2016
• Last Updated: January 26, 2023
• Results First Posted: April 30, 2021

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share

Locations

US (4); CA (1); DK (1)